Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia

Costanza Emanueli, Alessandra Minasi, Antonella Zacheo, Julie Chao, Lee Chao, Maria Bonaria Salis, Stefania Straino, Maria Grazia Tozzi, Robert Smith, Leonardo Gaspa, Giuseppe Bianchini, Francesco Stillo, Maurizio C. Capogrossi, Paolo Madeddu

Research output: Contribution to journalArticlepeer-review

Abstract

Background - Human tissue kallikrein (HK) releases kinins from kininogen. We investigated whether adenovirus-mediated HK gene delivery is angiogenic in the context of ischemia. Methods and Results - Hindlimb ischemia, caused by femoral artery excision, increased muscular capillary density (P1 receptor gene (P1 receptors blunted ischemia-induced angiogenesis (P2 receptor antagonism was ineffective. Intramuscular delivery of adenovirus containing the HK gene (Ad.CMV-cHK) enhanced the increase in capillary density caused by ischemia (969±32 versus 541±18 capillaries/mm 2 for control, P1 or B 2 receptors prevented HK-induced angiogenesis. Conclusions - HK gene delivery enhances the native angiogenic response to ischemia. Angiogenesis gene therapy with HK might be applicable to peripheral occlusive vascular disease.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalCirculation
Volume103
Issue number1
Publication statusPublished - Jan 9 2001

Keywords

  • Angiogenesis
  • Bradykinin
  • Gene therapy
  • Ischemia
  • Muscles

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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